Acute presentations of inherited metabolic disease in adulthood.

Clinical Medicine Vol 8 No 6 December 2008 621 © Royal College of Physicians, 2008. All rights reserved. It has been over a century since Sir Archibald Garrod first recognised the existence of inherited metabolic diseases (IMD).1 Technological and scientific advances have gradually led to greatly increased understanding of their aetiology and pathogenesis, and have ultimately resulted in effective therapies. Treatment has dramatically altered the natural history of metabolic disorders. Examples include: • the phenylalanine-restricted diet for phenylketonuria2 • uncooked cornstarch for the hepatic glycogenoses3 • cobalamin for vitamin B12responsive methylmalonic acid4 • nitisinone for tyrosinaemia type 15 • enzyme replacement therapy for Gaucher disease.6 Not only can more than ever before be done today for patients but, as laboratory technology improves, more individuals with IMD are being diagnosed. Thin layer chromatography, high-peformance liquid chromatography, gas chromatographymass spectrometry and tandem mass spectrometry (TMS) have successively led to easier screening (both primary and secondary), making diagnoses that were previously missed. Paediatric metabolic medicine has achieved its aims: • to prevent untreatable disease with genetic counselling and antenatal testing • the provision of effective therapy to children with IMDs so that they can survive childhood and integrate into society. Affected individuals can also present for the first time in adulthood. It is important for clinicians working in the adult sector to be aware of these disorders, not only to manage survivors of childhood but also to recognise patients presenting in adulthood. This article describes some acute clinical scenarios in which IMDs need to be considered. As they are genetic diseases, missing the diagnosis may have implications both for the affected individuals and for their families.